Stem cells have been defined as multipotent, self-renewing cells with the potential to differentiate into multiple cell types. Cancer stem cells (CSCs) are cancer cells (found within tumors or hematological cancers) that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. CSCs are therefore tumorigenic (tumor-forming), perhaps in contrast to other non-tumorigenic cancer cells. John Dick and his coworkers identify the first cancer stem cell, the leukaemia stem cell (Nature Med. 1997 3, 730-737). The first stem cell identified from a solid tumor is the breast cancer stem cell (Proc. Natl. Acad. Sci. USA 2003 100, 3983-3988). CSCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types. Such cells are proposed to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. Therefore, development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients, especially for patients with metastatic disease.
The CSCs contain an increased number of multi-drug resistant transporter proteins which pump out chemotherapeutic drugs from the cells. Also, the CSCs were shown to be more resistance to radiation. CSCs comprise a unique subpopulation (often 0.1-10% or so) of a tumor that, relative to the remaining 90% or so of the tumor (i.e., the tumor bulk), are more tumorigenic, relatively more slow-growing or quiescent, and often relatively more chemoresistant than the tumor bulk. Given that conventional therapies and regimens have, in large part, been designed to attack rapidly proliferating cells (i.e. those cancer cells that comprise the tumor bulk), cancer stem cells which are often slow-growing may be relatively more resistant than faster growing tumor bulk to conventional therapies and regimens. A population of CSCs, which gave rise to it, could remain untouched and cause a relapse of the disease.
U.S. Pat. No. 8,846,633 provides a method for inhibiting cancer stem cell like properties and chemoradioresistant properties of cancer or tumor cells comprising delivering miR145 to the cancer or tumor cells, particularly brain tumor and head and neck cancer cells. US 20140045841 provides a method for inhibiting the growth of cancer stem cells, particularly colorectal cancer stem cells, liver cancer stem cells, lung cancer stem cells or breast cancer stem cells, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of antimycin A or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier. Cancer stem cells by virtue of their chemoresistance may contribute to treatment failure, and may also persist in a patient after clinical remission and these remaining cancer stem cells may therefore contribute to relapse at a later date. Accordingly, new therapeutic agents and/or regimens designed to target cancer stem cells are needed.